Abstract 4917: Establishment of patient-derived lung epithelial progenitor lines as a foundation for autologous immune and tumor modeling

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Resistance to immunotherapy significantly limits durable clinical benefit. Elucidating the interactions between epithelial and immune compartments within the lung tumor microenvironment is critical for the development of effective interventions. However, most preclinical systems do not preserve patient-specific epithelial programs or support autologous immune modeling.The purpose of this study was to generate and characterize patient-derived lung epithelial progenitor lines from uninvolved tissues of lung cancer patients as a foundation for future immune and tumor co-culture platforms. Epithelial progenitor organoids were established from uninvolved lung tissues of adenocarcinoma and squamous cell carcinoma patients and maintained to passage 5 (P5) under defined, growth factor–optimized conditions. Identity and quality were verified by pan-cytokeratin immunostaining and fibronectin. Progenitor lines were expanded and cryopreserved to create a biobank supporting downstream air–liquid interface (ALI) and immune co-culture assays. Parallel spatial imaging of matched tumor and uninvolved tissues, along with RNA sequencing of progenitor cell lines, will be performed to analyze the immune and stromal architecture, providing integrative context for model development.Sixteen stable progenitor lines were generated (7 female, 9 males; 9 adenocarcinoma, 7 squamous cell carcinoma) with consistent morphology and long-term viability. Cryopreserved stocks and associated patient-matched materials (tumor blocks, uninvolved tissues, PBMCs, and serum) are now being integrated into functional ALI and immune co-culture assays.In conclusion, this work establishes a comprehensive biobank of lung epithelial progenitor lines derived from cancer-adjacent tissues, enabling next-generation autologous models to explore immune regulation, aging, and therapeutic resistance in lung cancer. Citation Format: Sanaz Keshavarz Shahbaz, Florentina Marches, Te-Chia Wu, Mohammed Toufiq, Andrew Salner, Peter Yu, Adolfo Garcia-Sastre, Karolina Palucka. Establishment of patient-derived lung epithelial progenitor lines as a foundation for autologous immune and tumor modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4917.